The objectives of this proposal are investigations of the enzyme delta 4-3-ketosteroid-5 alpha-oxidoreductase obtained from the rat ventral prostate and the androgen dependent Dunning R3327 adenocarcinoma of prostatic origin. The proposed studies include the preparation of hormone analogs as probes of the substrate specificity of the 5 alpha-reductase derived from the normal and transformed tissues. Further investigations include the preparation of active-site generated irreversible inhibitors of the reductase as metabolic blockers of the biosynthesis of dihydrotestosterone. The competitive reversible and irreversible inhibitors will be kinetically evaluated in both the normal and transformed tissues in order to determine any differences in the specificity or kinetic parameters of the enzyme from the different sources. Inhibitory analogs will then be tested in vivo for effects on the 5 alpha-reductase and growth patterns of the prostate as determined by wet weight determination as well as DNA synthesis. The data obtained from the proposed studies will be useful in understanding the role of 5 alpha-reductase in normal and abnormal prostatic growth. In addition the potential irreversible inhibitors would be beneficial in the control of hormonally dependent carcinoma of the prostate.